Complications of cyclosporin therapy.

Abstract

AbstractCyclosporin (CsA) therapy has improved the outcome of allotransplants. Because of a relatively selective action on T lymphocytes, CsA therapy causes fewer immunosuppressive complications of infection or malignancy compared to previous chemical agents, which were relatively nonspecific in their spectrum of action on lymphoid versus nonlymphoid cells. Gastrointestinal complaints after oral administration and vasomotor reactions after intravenous administration represent pharmacologic toxicities rarely of major clinical import. Drug‐induced complications involve primarily the neuroectodermal, or the mesenchymal hepatic and renal, systems. While the former group of complications are rarely severe, mesenchymal nephrotoxicity poses a major limitation of drug therapy. On the one hand, reductions by 33% of normal renal function in patients treated with CsA for autoimmune disease appear to be reversible on discontinuance of therapy. On the other hand, severe renal dysfunction occurs in transplant recipients, particularly in the presence of concomitant therapy with nephrotoxic drugs. In the kidney transplant setting, numerous factors exacerbate the druginduced injury, including adverse donor procurement conditions, prolonged graft storage, and allograft rejection. Since the clinical and histologic findings in CsA nephrotoxicity tend to be pleiomorphic, no single diagnostic or therapeutic strategy has emerged. However, insights gained through pharmacologic monitoring of renal allograft recipients suggest that the group at increased risk for nephrotoxicity can be identified by elevated serum drug trough levels, increased area under the plasma time concentration curve, prolonged elimination half‐life, and heightened pharmacodynamic sensitivity to CsA. Analysis of pharmacologic data in conjunction with clinical results should provide drug regimens of maximal therapeutic index with minimal risk of complications.